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Title: DhHP-6 ameliorates hepatic oxidative stress and insulin resistance in type 2 diabetes mellitus through the PI3K/AKT and AMPK pathway. Author: Wang K, Liang Y, Su Y, Wang L. Journal: Biochem J; 2020 Jun 26; 477(12):2363-2381. PubMed ID: 32510127. Abstract: Insulin resistance is one major features of type 2 diabetes mellitus (T2DM). Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6), a novel microperoxidase mimetic designed and synthesized based on microperoxidase 11 (MP-11), can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we showed that oral DhHP-6 could reduce blood glucose and improve insulin resistance. To investigate the mechanisms of how DhHP-6 ameliorates oxidative stress and insulin resistance, we established T2DM mouse models and glucosamine-induced HepG2 cell insulin resistance models. The results suggested that DhHP-6 decreased blood glucose, increased antioxidant enzyme activity, and inhibited glycogen synthesis in T2DM mice. In addition, DhHP-6 improved insulin resistance by activating phosphatidylinositol 3-kinase (PI3K)/AKT, and AMP-activated protein kinase (AMPK) pathway in T2DM mice. Furthermore, DhHP-6 also activated PI3K/AKT and AMPK pathway in glucosamine-induced HepG2 cells. However, LY294002 did not completely inhibit AKT phosphorylation, and partially inhibited AMPK phosphorylation, whilst compound C only partially reduced AMPK phosphorylation, and also partially inhibited AKT phosphorylation, suggesting that AKT and AMPK interact to improve insulin resistance. Thus, these data suggest that DhHP-6 attenuates insulin resistance via the PI3K/AKT and AMPK pathway.[Abstract] [Full Text] [Related] [New Search]